重组人血管内皮抑素联合放疗对Lewis肺癌小鼠碳酸酐酶Ⅸ和钙粘连蛋白表达的影响

Effect of recombinant human Endostar combined with radiotherapy on expression of carbonic anhydrase Ⅸ and E-cadherin in Lewis lung cancer xenograft model

目的:观察重组人血管内皮抑素(Endostar)联合放射治疗(简称放疗)对Lewis肺癌小鼠碳酸酐酶Ⅸ(CAⅨ)和钙粘连蛋白(E-cadherin,E-cad)表达的影响,进一步探讨Endostar对放疗的协同增敏机制。方法:建立Lewis肺癌小鼠模型,随机分为空白对照组、Endostar组、放疗组、Endostar联合放疗组,分别予以相应干预后观察各组移植瘤生长情况。治疗结束后第1天摘除小鼠眼球采血,用RT-PCR检测各组血清中CAⅨ和E-cad mRNA表达情况。结果:(1)随着时间延长,与空白对照组比较,Endostar组和放疗组移植瘤体积变化差异无统计学意义(P>0.05),Endostar联合放疗组肿瘤体积变化差异有统计学意义(P<0.05)。(2)Endostar组、放疗组和Endostar联合放疗组CAⅨ表达均较空白对照组降低(P<0.05),Endostar联合放疗组下降更明显(P<0.05)。(3)Endostar组、放疗组和Endostar联合放疗组E-cad mRNA表达均较空白对照组增加(P<0.05),Endostar联合放疗组与放疗组、Endostar组比较,E-cad mRNA表达增加,差异有统计学意义(P<0.05)。结论:Endostar具有放射增敏作用,Endostar联合放疗能明显抑制Lewis肺癌移植瘤的生长,这种作用可能是通过下调CAⅨmRNA、上调E-cad mRNA表达,改善瘤体局部乏氧状态和增加氧供实现的。

To investigate the effect of recombinant human Endostar combined with radiotherapy on the expression of carbonic anhydrase Ⅸ and E-cadherin（E-cad） in Lewis lung cancer xenograft model and explore the potential collaborative mechanism of the combination of therapy. Methods： Lewis lung cancer xenograft model was established by subcutaneously injecting Lewis lung cancer cells in the left hind of C57BL/6 mice. Thirty-two tumorbearing mice were randomly divided into 4 groups： control group, Endostar group, radiation therapy group, and Endostar combined with radiotherapy. From the day of treatment beginning, tumor volume was calculated and tumor vernier caliper was drawn. At day one after the treatment,blood was taken from eyes for RT-PCR which was used to detect the expression of CA Ⅸ and E-cad mRNA. Results： （1） With the prolonged,compared with control group, was tumor volume of Endostar group and radiation therapy group had no difference （ P 〉 0.05 ）, but significance seen in Endostar combined with radiotherapy group （P 〈0.05）. （2） The expression of CAIN in Endostar group,radiation therapy group and Endostar combined with radiotherapy group significantly lower than that of control group （ P 〈 0.05 ） ;the lowest was in Endostar combined with radiotherapy group. （3） The expression of E-cad mRNA in Endostar group,radiation therapy group and Endostar eombined with radiotherapy group somewhat higher than that of control group （P 〈 0.05 ）, compared with radiation therapy group group and Endostar group, the difference were statistically significant in Endostar combined with radiotherapy group （P 〈 0.05 ）. Conclusions： Endostar concurrent radiaotherapy can inhibite the growth of Lewis lung cancer,which might be achieved through down-regulation CAⅨ mRNA and up-regulation E-cad mRNA expression to improve tumor local hypoxia and increase oxygen supply.